The researchers have identified a potential genetic target for treating an especially painful and invasive form of endometriosis.

Their study published in Cell Reports, a scientific journal, could lead to better treatments for women suffering from severe forms of endometriosis, said a first co-author of the study.

Their research focused on a type of endometriosis that occurs in women who have a mutation in a gene called ARID1A, which is linked to the more invasive and painful form of the disease. When ARID1A is mutated, so-called "super-enhancers," a part of the DNA that determines the function of cells, run wild, the co-author said. This allows the cells that normally line the uterus to form deep implants outside the uterus and cause severe pelvic pain.

"There haven't been many successful nonhormonal therapies for this form of endometriosis that have made it to the bedside yet," the author said.

In laboratory experiments, the authors tested a drug that appeared to target the super-enhancers and stop the spread of endometriosis. Such a drug -- part of a new type of treatment called "epigenetic therapy" that controls how genes are expressed -- could be far more effective than current treatments, including surgery, hormone therapy and pain management.

Endometriosis, particularly the kind associated with the ARID1A mutation, can be debilitating for many women, often leading to infertility.

"It can seriously impact women's quality of life and their ability to have a family and work," said the senior author the study. "It's not easy to treat, and it can become resistant to hormone therapy. The most clinically impactful thing we found is that targeting super-enhancers might be a new treatment for this deeply invasive form of the disease."

The drug they studied targeted a protein in cells called P300, suppressing the super-enhancers and offsetting the effects of the ARID1A mutation, the lead said. The same type of treatment could be used to treat other forms on endometriosis, the author said.

The researchers already are planning follow-up studies to find other drugs that could target P300, the first co-authors said.

https://msutoday.msu.edu/news/2020/genetic-target-endomitriosis

https://www.cell.com/cell-reports/fulltext/S2211-1247(20)31355-3

http://sciencemission.com/site/index.php?page=news&type=view&id=publications%2Farid1a-mutations&filter=22